Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients.
A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been observed repeatedly in Crohn disease (CD) patients. In this study, we determined the composition of the mucosa-associated microbiota of CD patients at the time of surgical resection and 6 months later using FISH analysis. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CD. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-kappaB activity, F. prausnitzii had no effect on IL-1beta-induced NF-kappaB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-gamma production levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis, as demonstrated by real-time quantitative PCR (qPCR) analysis. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-kappaB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment.
Sokol
Harry
H
Unité Ecologie et Physiologie du Système Digestif, Institut National de la Recherche Agronomique U910, Domaine de Vilvert, 78350 Jouy-en-Josas, France.
Pigneur
Bénédicte
B
Watterlot
Laurie
L
Lakhdari
Omar
O
Bermúdez-Humarán
Luis G
LG
Gratadoux
Jean-Jacques
JJ
Blugeon
Sébastien
S
Bridonneau
Chantal
C
Furet
Jean-Pierre
JP
Corthier
Gérard
G
Grangette
Corinne
C
Vasquez
Nadia
N
Pochart
Philippe
P
Trugnan
Germain
G
Thomas
Ginette
G
Blottière
Hervé M
HM
Doré
Joël
J
Marteau
Philippe
P
Seksik
Philippe
P
Langella
Philippe
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002478:Cells, Cultured; D003092:Colitis; D003424:Crohn Disease / Q000382:microbiology / Q000628:therapy*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology*; D007962:Leukocytes / Q000276:immunology / Q000382:microbiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D019936:Probiotics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D045857:Ruminococcus / Q000302:isolation & purification*; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B